Myelin basic protein-specific and TCR V beta 8.2-specific T-cell lines from TCR V beta 8.2 transgenic mice utilize the same V alpha and V beta genes: specificity associated with the V alpha CDR3-J alpha region.

Our analysis of TCR V gene usage in mice transgenic for the V beta 8.2 gene has demonstrated that T cells isolated from the spinal cord of these transgenic mice during active experimental autoimmune encephalomyelitis were significantly biased for V alpha 2 expression. This V alpha 2 bias was noted in T cells derived from the periphery as well but only after stimulation with specific antigen. Thus, spinal cord-derived pathogenic T cells had already undergone activation and expansion within the central nervous system environment of these mice. As part of an investigation of regulatory function in these V beta 8.2 transgenic mice, two T cell lines were selected. The first T cell line is encephalitogenic and specific for the dominant myelin basic protein peptide NAc1-11, while the second T cell line is specific for the V beta 8.2 protein. Surprisingly, polymerase chain reaction and sequence analysis of the TCR from both the T cell lines demonstrated that they utilize identical V beta, D beta, J beta, and V alpha gene segments. The only difference found was in their use of the J alpha gene segment, indicating that this region of the TCR molecule can play a key role in determining antigen specificity.